PROLACTIN-SECRETING PITUITARY TUMOR
Prolactin-secreting pituitary tumors (prolactinomas) are the most common hormone-secreting pituitary tumor. They are monoclonal lactotroph cell adenomas that appear to result from sporadic mutations. Although most prolactinomas are sporadic, they are the most frequent pituitary tumor in persons with multiple endocrine neoplasia type 1 (see Plate 8-1). In addition, more than 99% of prolactinomas are benign. Approximately 10% of prolactin-secreting pituitary tumors cosecrete growth hormone because of a somatotroph or mammosomatotroph component.
In women, the typical clinical presentation of a prolactin-secreting microadenoma (10 mm in largest diameter) is secondary amenorrhea with or without galactorrhea. But in men, because of the lack of symptoms related to small prolactinomas, a prolactinoma is not usually diagnosed until the tumor has enlarged enough to cause mass-effect symptoms. This late diagnosis is also the typical clinical scenario in post-menopausal women. Mass-effect symptoms of prolactin-secreting macroadenomas include visual ﬁeld defects with suprasellar extension, cranial nerve palsies with lateral (cavernous sinus) extension (e.g., diplopia, ptosis), headaches, and varying degrees of hypopituitarism with compression of the normal pituitary tissue.
Hyperprolactinemia results in decreased gonadotropin secretion in men and women. In men, hypogonadotropic hypogonadism causes testicular atrophy, low serum testosterone concentrations, decreased libido, sexual dysfunction, decreased facial hair growth, and decreased muscle mass. Because men lack the estrogen needed to prepare breast glandular tissues, they rarely present with galactorrhea. In premenopausal women, however, hyperprolactinemia may cause bilateral spontaneous or expressible galactorrhea (see Plate 4-26). In addition, prolactin-dependent hypogonadotropic hypogonadism in women results in secondary amenorrhea and estrogen deﬁciency symptoms. Long-standing hypogonadism in both men and women may lead to osteopenia and osteoporosis.
In general, the blood concentration of prolactin is proportionate to the size of the prolactinoma. For example, a 5-mm prolactinoma is associated with serum prolactin concentrations of 50 to 250 ng/mL (reference range, 4–30 ng/mL), but prolactinomas larger than 2 cm in diameter are associated with serum prolactin concentrations greater than 1000 ng/mL. However, there are exceptional cases of small prolactinomas that have extremely efﬁcient prolactin secretory capacity (e.g., serum prolactin concentration 1000 ng/mL) and cases of the converse—very inefﬁcient prolactin-secreting macroadenomas (e.g., serum prolactin concentrations 200 ng/mL).
Treatment decisions in patients with prolactin-secreting pituitary tumors are guided by the signs and symptoms related to hyperprolactinemia and mass-effect symptoms related to the sellar mass. For example, a 4-mm prolactin-secreting microadenoma detected incidentally in an asymptomatic postmenopausal woman may be observed without treatment. However, because prolactin-secreting pituitary macroadenomas grow over time, treatment is almost always indicated for macroprolactinomas even if the patient lacks tumor-related symptomatology. When treatment is indicated (e.g., if secondary hypogonadism is present in men or in premenopausal women or if a macroadenoma is present), an orally administered dopamine agonist (e.g., cabergoline or bromocriptine) is the treatment of choice. Dopamine agonists are very effective in promptly normalizing the serum prolactin concentration and reducing the size of the lactotroph adenoma. After initiating a dopamine agonist, the serum prolactin concentration should be monitored every 2 weeks, and the dosage of bromocriptine or cabergoline should be increased until the prolactin levels decrease into the reference range. Approximately 3 to 6 months after achieving a normal serum prolactin concentration, pituitary-directed magnetic resonance imaging (MRI) should be performed to document tumor shrinkage. The minimal dosage of the dopamine agonist that results in normoprolactinemia should be continued indeﬁnitely. In a small percentage of patients, prolactin-secreting adenomas may be cured with longterm dopamine agonist therapy. Thus, a periodic (e.g., every 2 years) 2-month holiday off the dopamine agonist is indicated to determine whether hyperprolactinemia recurs. Patients with macroprolactinomas that have sphenoid sinus extension should be cautioned about the potential for cerebrospinal ﬂuid (CSF) rhinorrhea that may occur as the tumor shrinks. CSF rhinorrhea requires an urgent neurosurgical procedure to prevent the development of pneumocephalus and bacterial meningitis. When patients are intolerant of the dopamine agonist (e.g., nausea, lightheadedness, mental fogginess, or vivid dreams) or if the tumor is resistant to this form of therapy, transsphenoidal surgery or gamma knife radiation therapy may be considered.